Dr. Gibbons is a Board Certified Neurologist with fellowship training in neurophysiology. Dr. Gibbons works at Beth Israel Deaconess Medical Center (BIDMC) and is Director of the Peripheral Neuropathy Center at Joslin Diabetes Clinic. Dr. Gibbons'interest in diabetic neuropathy began during residency at Johns Hopkins Hospital and has continued at BIDMC with an NIH NRSA grant investigating diabetic neuropathy with Dr. Roy Freeman. Dr. Gibbons plans to remain in academic medicine and, with the mentorship of Dr. Freeman, will focus his career towards the investigation and treatment of diabetic neuropathy and its role in wound healing. Neuropathy will develop in up to sixty percent of patients with diabetes and leads to an unacceptably high rate of morbidity and mortality. Potential complications from diabetic neuropathy include pain, ulceration and amputation which are consequences of myelinated and unmyelinated nerve fiber dysfunction. The interactions between cutaneous small fiber autonomic and sensory nerves play a crucial role in ulcer development and healing. Damage to cutaneous autonomic nerve fibers leads to reduced sweat production and development of dry, cracked skin;a potential nidus for infection. Damage to small sensory nerve fibers reduces axon reflex vasodilation, a critical component to neurogenic inflammation and wound healing. Dysfunction of both autonomic and sensory small nerve fibers reduces wound healing capacity and increases risks of both cutaneous infection and ulceration. The objective of this application is 1) to develop a novel human model of diabetic autonomic neuropathy, 2) to determine factors underlying vasomotor reactivity in small fiber neuropathy, and 3) to identify the autonomic-sensory small nerve fiber interactions associated with impaired wound healing in patients with diabetes. The central hypothesis of this application is that discovery of the mechanisms underlying the autonomic-sensory interactions in diabetic small fiber neuropathy will improve current and future treatments of diabetic patients with impaired wound healing. Development of human models of neuropathy and wound healing will greatly increase our knowledge of the effects of diabetes on nerve function and improve our ability to predict responses to novel treatments. These human models of autonomic neuropathy and wound healing will improve our ability to predict, treat and reduce complications of ulceration and amputation in patients with diabetes.